Numerous disease processes cause inner ear dysfunction and represent an opportunity for therapeutic intervention. Hearing loss is the common endpoint of many inner ear disorders including presbycusis, sudden sensorineural hearing loss, genetic diseases, trauma, exposure to noise and ototoxic medications, and autoimmune inner ear disease. Inner ear disorders causing balance dysfunction include Meniere's disease, benign positional vertigo, and labyrinthitis. Therapeutic strategies to treat inner ear diseases include delivery of medications (systemically and locally), surgical intervention, sound amplification (with hearing aids), and physical therapy. This paper will focus on the pharmacologic management of inner ear disease and specifically will focus on the strategies used to deliver drugs for treatment of inner ear disease. The intent of this paper is not to perform an exhaustive review of the pharmacologic management of all forms of inner ear disease; rather, specific diseases and therapeutics will be used as examples to highlight the approaches and devices utilized to deliver drugs to the inner ear. The goals of the paper are to review the historical basis for management of inner ear disease using drug delivery techniques, to review the past and present strategies used to delivery drugs to the inner ear, to highlight the potential strengths and weaknesses of drug delivery techniques for treatment of inner ear disease, and to provide insight into novel and innovative strategies to achieve delivery of drugs directly into the inner ear. The overarching purpose of this paper is to review the current status of knowledge on drug delivery for treatment of inner ear disease and to provide insight into the potential future of the field.
Therapeutic management of inner ear disease is undergoing a paradigm shift. The first treatments for control of inner ear disease, including aminoglycosides for bilateral Meniere's disease and steroids for sudden sensorineural hearing loss, were delivered systemically. The systemic route for delivery of medication is accompanied by some troubling drawbacks, including variable penetration into the inner ear due to the presence of a blood-cochlea barrier and the potential for undesirable systemic side effects. Intratympanic drug delivery for inner ear therapy avoids some of the problems associated with systemic delivery and has now become a routine strategy for treating inner ear disease. The development of adjunctive devices and carrier mechanisms are active areas of research focused on improving drug delivery via the intratympanic route. Potential drawbacks of intratympanic drug delivery include anatomic barriers to absorption at the round window membrane, loss of drug down the Eustachian tube, and variable or unknown pharmacokinetic profiles of medications currently delivered via this route. Most recently, approaches to drug delivery have focused on bypassing the middle ear altogether and delivering medications directly to the inner ear. Direct therapy to the inner ear could have applications ranging from delivery of currently available drugs with undesirable systemic side effects to delivery of steroids or neurotrophins with cochlear implantation to novel gene- or stem cell-based therapies. Recent technological advancements in emerging fields such as microfluidics and microsystems technologies permit the development of drug delivery systems designed to deliver drugs directly to the inner ear over a sustained period of time. To understand the contemporary focus on local strategies for management of inner ear disease, one must understand the systemic therapeutic route and its drawbacks.